This proposal requests funding for the purchase of a Zeiss Z.1 Lightsheet Microscope at the University of Kentucky, which will be housed in a new Imaging Center operated by the College of Arts and Sciences Biology Department. This instrument would be the first of its kind in the state of Kentucky. The lightsheet microscope incorporates state-of-the-art technology that will allow users to conduct long-term time-lapse imaging of live specimens, as well as to image whole fixed, cleared tissues at subcellular resolution. Lightsheet microscopy has several advantages over conventional fluorescence microscopy techniques, including greater sample penetration depth, faster image acquisition times, superior signal-to-noise ratio, and significantly reduced exposure, which minimizes photobleaching and toxicity. This equipment will serve a growing group of NIH-funded investigators in the Biology department studying developmental and regenerative processes in a variety of model organisms (mouse, zebrafish, salamander, lamprey, and fly) whose research will be greatly enhanced by the ability to conduct live cell and tissue imaging. It will also serve scientists located in the neighboring Colleges of Medicine, Agriculture, and Pharmacy. Research areas that will be enhanced through the acquisition of this lightsheet microscope include studies of germ cell and organ system development, tissue regeneration, circadian rhythms, the role of scaffolding proteins in hematopoiesis, and the regulation of signaling pathways during development.